• Clinical science

Oral anticoagulants

Summary

Anticoagulants are used for treating and preventing embolic events. The most common oral anticoagulatory agents are vitamin K antagonists such as warfarin (Coumadin®) and phenprocoumon. Non-vitamin K antagonist oral anticoagulants (NOACs) like dabigatran and rivaroxaban have also gained popularity in recent years. Vitamin K antagonists inhibit the enzyme vitamin K epoxide reductase, thereby blocking hepatic synthesis of the active, reduced form of vitamin K (needed for carboxylation of coagulation factors II, VII, IX, and X, protein C, protein S). This effect can last for several days, which complicates exact dosing and makes regular monitoring necessary. Vitamin K antagonists are also metabolized by C-P450 (CYP) enzymes and therefore interact with a broad range of foods and drugs. NOACs act selectively via inhibition of thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban, edoxaban). Because of their comparatively short half-life and fewer interactions, NOACs are easier to control and administer than warfarin and do not require regular monitoring to ensure their efficacy and safety. There are no established tests for monitoring overdosing since the usual coagulation studies (aPTT, factor Xa activity) can yield false results. For all substances, it is important to consider the dose-dependent risk of bleeding, especially when combining different substances that affect hemostasis (e.g., aspirin, clopidogrel, ticagrelor).

Overview

Overview of commonly used oral anticoagulants

Substances Mechanism of action
Advantages Disadvantages
Vitamin K antagonists (coumarins)

Phenprocoumon

Warfarin

  • Well-known effects and side effects
  • Low costs
  • In cases of life-threatening bleeding: direct reversal by replacement (e.g., prothrombin complex concentrate, FFP) or indirect/delayed reversal by increasing production of coagulation factors (e.g., vitamin K)
Direct oral anticoagulants
Direct oral thrombin inhibitors

Dabigatran

  • Costly
  • Limited clinical experience with these drugs
  • Not recommended, and partially contraindicated, in patients with artificial cardiac valves
  • Not suited for patients with valvular atrial fibrillation
Direct oral factor Xa inhibitors

Apixaban

Rivaroxaban

Edoxaban

  • Selective and direct inhibition of factor Xa
General notes regarding oral anticoagulation
Indications for all oral anticoagulants

Expected laboratory changes

The most important side effect of all oral anticoagulants is a dose-dependent increase in bleeding risk!

References:[1][2][3][4][5]

Side effects

Coumarins

Individuals with protein C deficiency are at a higher risk of developing warfarin necrosis!

Direct factor Xa inhibitors and direct thrombin inhibitors

References:[1][6][7][8][9][10][11]

We list the most important adverse effects. The selection is not exhaustive.

Indications

Coumarins

Phenprocoumon

Warfarin

Direct thrombin inhibitors

Dabigatran

Direct factor Xa inhibitors

Apixaban

Rivaroxaban

Edoxaban

References:[12][13][14][15][16]

Contraindications

References:[17][18][19]

We list the most important contraindications. The selection is not exhaustive.

Interactions

Warfarin interactions

Warfarin is metabolized by cytochrome P450 (CYP) enzymes. Its effects can be significantly impacted by a variety of interactions; for this reason, warfarin serum levels should be monitored regularly.

P450 inducers: warfarin levels (Chronic Alcoholics Steal Phen-Phen and Never Refuse Greasy Carbs): C - Chronic alcohol use, S - St. John's wort, P - Phenytoin, P - Phenobarbital, N - Nevirapine, R - Rifampin, G - Griseofulvin, C - Carbamazepine

P450 inhibitors can be remembered with “sickfaces.com group”: S - Sulfonamides, I - Isoniazid, C - Cimetidine, K - Ketoconazole, F - Fluconazole , A - Alcohol (binge drinking), C - Ciprofloxacin, E - Erythromycin, S - Sodium valproate, C - Chloramphenicol, O - Omeprazole, M - Metronidazole, G - Grapefruit juice
References:[20][21][22]

Guidelines & therapy recommendations

References:[23]